This project is designed to investigate the cellular immune responses of sporadic patients with multiple sclerosis (MS) in both the autologous mixed lymphocyte response and the response to measles virus. Abnormalities in both these reponses have previously been described in MS. Here, particular attention is to be given to fluctuations in these responses which might correlate with disease activity. The lymphoproliferative response, its kinetics and the possible cross-reactivities of responder cells will be investigated. Responder cell phenotypes and genetic restrictions will be identified in conjunction with in vitro assays. The capacity of these responder cells to generate effector cells such as antigen-specific cytotoxic lymphocytes (CTL) will be studied using measles virus-infected or haptenmodified cells as stimulators and target cells. The production of Interleukins 1 and 2 as well as CTL differentiation factors and the induction of lymphokine receptors in the generation of these cellular responses will also be studied. Further, the interactions between the cells involved in the generation and the regulation of these responses will be investigated. Particular attention will be paid to the effects of T cell help or suppression in the initiation of these responses, and their subsequent modulation. These studies are designed to test the hypothesis that multiple sclerosis is an autoimmune disease by studying the generation of effector T cells and regulatory circuits for antigen specific T cell responses. Information gained from this project may potentially assist in defining etiologic or pathogenetic factors of importance in the disease. This may have later relevance to the development of more rational immunotherapies for MS.